This proposal is a request for funding to study the total synthesis of the recently discovered antitumor antibiotic quinocarcin (1,DC-52). Being the simplest member of the saframycin/naphthyridinomycin class of antibiotics, the synthetic protocol developed will focus on the asymmetric preparation of the isoquinoline nuclei and the bicyclic piperazines such that synthetic entries to naphthyridinomycin will be realized. It is the purpose of this proposal to establish the functional significance of the bicyclic piperazine moiety in imparting chemical stability manifested as biological reactivity in the DC-52 molecule. A mechanism of action is proposed and synthetic protocol will be established to probe both the covalent modification of DNA as well as the reported oxygen-dependent DNA strand scission by DC-52.